IV. Action of tachykinins on gastric chief cells. The cellular basis of the ability of the tachykinins (substance P, neurokinin A, neurokinin B) to cause pepsinogen release was investigated in isolated, enriched chief cells from guinea pig stomach. These peptides were found by binding studies to interact only with a NK1 receptor subtype. The receptor had high and low affinity states. The ligand was rapid internalized after binding and the internalization rate was altered by agents that activated phospholipase C, PKC or adenylate cyclase. Activation of NK1 receptors resulted in PLC activation. Correlation of the ability of a number of tachykinins ability to occupy the receptor and cause pepsinogen release suggested that occupation of the low affinity NK, state resulted in activation of the NK1 receptor.